FLORITAS

Quick Overview

Our aim is to reach out to the globe within shortest possible time frame.

To promote this objective, not only we distribute and market our Urology range of products globally through our distribution channels but we also undertake ‘contract manufacturing’& ‘formulation development ’of our wide range of generic products such as Floritas which contains Tamsulosin Hydrochloride BP.... 400 mcg.

The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck.

Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.

Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in the human prostate. At least three discrete alpha1 adrenoceptor subtypes have been identified: alpha1A, alpha1B, and alpha1D; their distribution differs between human organs and tissue. Approximately 70% of the alphal receptors in the human prostate are of the alpha1A subtype.

Tamsulosin HCI capsules are not intended for use as an antihypertensive drug.

Urologicpharmacodynamics effects have been reported in neurologically impaired pediatric patients and in adults with BPH.

PHARMACOKINETICS:

Absorption: Absorption of tamsulosin hydrochloride from Tamsulosin HCI capsules 400 mcg is essentially complete (>90%) following oral administration under fasting conditions. Tamsulosin hydrochloride exhibits linear kinetics following single and multiple dosing, with achievement of steady-state concentrations by the fifth day of once-a­day dosing.

The binding of tamsulosin hydrochloride to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, tamsulosin hydrochloride had no effect on the extent of binding of these drugs.

Metabolism: Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged.

However, the pharmacokinetic profile of the metabolites in humans has not been established. Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6 as well as via some minor participation of other CYP isoenzymes.

Inhibition of hepatic drug-metabolizing enzymes may lead to increased exposure to tamsulosin. The metabolites of tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate priorto renal excretion.

Excretion: Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of tamsulosin hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with Tamsulosin HCI capsules, the apparent half-life of tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.

Tamsulosin HCI capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Tamsulosin HCI capsules are not indicated for the treatment of hypertension.

DOSAGE AND ADMINISTRATION:

Tamsulosin HCI capsules 400 mcg once daily is recommended as the dose for the treatment of the signs and symptoms of BPH. It should be administered approximately one-half hour following the same meal each day. For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of Tamsulosin HCI capsules can be increased to 0.8 mg once daily. Tamsulosin HCI capsules 400 mcg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole). If Tamsulosin HCI capsules administration is discontinued or interrupted for several days at either the 400 mcg or 800 mcg dose, therapy should be started again with the 0.4 mg once- daily dose.

CONTRAINDICATIONS:

Tamsulosin HCI capsules are contraindicated in patients known to be hypersensitive to tamsulosin hydrochloride or any component of Tamsulosin HCI capsules. Reactions have included skin rash, urticaria, pruritus, angioedema, and respiratory symptoms.

WARNINGS AND PRECAUTIONS:

Orthostasis

The signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were detected more frequently in Tamsulosin HCI capsule-treated patients.

As with other alpha adrenergic blocking agents there is a potential risk of syncope.

Patients beginning treatment with Tamsulosin HCI capsules should be cautioned to avoid situations in which injury could result should syncope occur.

Priapism

Rarely (probably less than 1 in 50,000 patients), tamsulosin, like other alpha1 antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition.

Screening for Prostate Cancer

Prostate cancer and BPH frequently co-exist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with Tamsulosin HCI capsules and at regular intervals afterwards.

Intraoperative Floppy Iris Syndrome

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha1 blockers, including Tamsulosin HCI capsules.

IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha1 blocker therapy prior to cataract surgery has not been established. The initiation of therapy with tamsulosin in patients for whom cataract surgery is scheduled is not recommended.

Sulfa Allergy

In patients with sulfa allergy, allergic reaction to Tamsulosin HCI capsules has been rarely reported. If a patient reports a serious or life threatening sulfa allergy, caution is warranted when administering Tamsulosin HCI capsules.

INTERACTIONS:

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.

The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tamsulosin HCI have not been evaluated.

The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of Tamsulosin HCI have not been evaluated.

The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with Tamsulosin HCI capsules have not been evaluated.

Cimetidine

Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of tamsulosin hydrochloride, which resulted in a moderate increase in tamsulosin hydrochloride AUC (44%).

Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between Tamsulosin HCI capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between Tamsulosin HCI capsules and other alpha adrenergic blocking agents may be expected.

PDE5 Inhibitors

Caution is advised when alpha adrenergic blocking agents, including Tamsulosin HCI, are co-administered with PDE5 inhibitors. Alpha adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension.

Warfarin

A definitive drug-drug interaction study between tamsulosin hydrochloride and warfarin was not conducted. Caution should be exercised with concomitant administration of warfarin and Tamsulosin HCI capsules.

Nifedipine, Atenolol, Enalapril

Dosage adjustments are not necessary when Tamsulosin HCI capsules are administered concomitantly with nifedipine, atenolol, or enalapril.

Digoxin and Theophylline

Dosage adjustments are not necessary when a Tamsulosin HCI capsule is administered concomitantly with digoxin ortheophylline. Furosemide

Tamsulosin HCI capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the Tamsulosin HCI capsules dosage.

PREGNANCY AND LACTATION:

Teratogenic Effects, Pregnancy Category B

Tamsulosin HCI capsules are not indicated for use in pregnant women.

Nursing Mothers

Tamsulosin HCI capsules are not indicated for use in lactating women.

USE IN SPECIFIC POPULATIONS

Geriatric Use

No overall differences in safety or effectiveness are observed in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Pediatric Use

Tamsulosin HCI capsules are not indicated for use in pediatric populations.

Renal Impairment

Patients with renal impairment do not require an adjustment in Tamsulosin HCI capsules dosing. However, patients with end-stage renal disease have not been studied.

Hepatic Impairment

Patients with moderate hepatic impairment do not require an adjustment in Tamsulosin HCI capsules dosage. Tamsulosin HCI has not been studied in patients with severe hepatic impairment.

Should overdosage of Tamsulosin HCI capsules lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, then administration of intravenous fluids should be considered.

If necessary, vasopressors should then be used and renal function should be monitored and supported as needed.

Studies done on the laboratory data indicate that tamsulosin hydrochloride is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.